Mode of action of GR69153, a novel catechol-substituted cephalosporin, and its interaction with the tonB-dependent iron transport system.
GR69153 is a novel cephalosporin incorporating a catechol-substituted 7-aminothiazolyl-oxime. The antibiotic is actively transported into gram-negative cells via iron-regulated outer membrane proteins regulated by the tonB product. This transport enhances bactericidal activity most significantly at low concentrations, essentially removing the permeability barrier for antibiotic uptake.
Silley
P
P
Chemotherapy Department, Glaxo Group Research Limited, Greenford, United Kingdom.
Griffiths
J W
JW
Monsey
D
D
Harris
A M
AM
D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000493:pharmacokinetics; D015636:Magnesium Chloride / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D013053:Spectrophotometry / Q000379:methods
D002352:Carrier Proteins; D002511:Cephalosporins; D002614:Chelating Agents; D007502:Iron Chelating Agents; D015636:Magnesium Chloride; C066944:GR 69153; D007501:Iron